Vasopressin V2 receptor (V2R)‐mediated potentiation of platelet activating factor (PAF)‐induced increase in rat mesentery venular microvessel permeability

Abstract

We tested the hypothesis that V2R activation potentiates the increase in microvessel permeability induced by PAF, an inflammatory mediator involved in sepsis. Individual venular microvessels in rat mesentery were perfused with 10mg/ml albumin in Ringer to measure hydraulic conductivity (Lp) by the modified Landis technique. The vessels were exposed to PAF (10nM), which induced an Lp increase peaking in 5–10min followed by return toward baseline values. The same vessels were then exposed to the selective V2R agonist desmopressin (dDAVP) for 40min followed by a second exposure to PAF in the presence of dDAVP. Peak PAF‐induced Lp significantly increased at dDAVP concentrations of 30pM (2.1 fold ±0.4 SEM, n=8) and 100pM (2.8 fold ±0.9 SEM, n=5) relative to peak Lp with PAF alone. In contrast, 10pM dDAVP did not increase PAF‐induced peak Lp. In control experiments, a second exposure to PAF alone did not cause an increase in peak Lp relative to the first PAF exposure. Also, dDAVP alone had no effect on baseline Lp. In further experiments, the V2R antagonist AdAc‐D‐Tyr(Et)‐Phe‐Val‐Asn‐Abu‐Pro‐Arg‐Arg‐NH2 (86nM) abolished potentiation by dDAVP (30pM) of PAF‐induced peak Lp (n=6). These results show that V2R activation potentiates PAF‐induced increase in vascular permeability, suggesting that V2R activation may exacerbate vascular leak syndrome in conditions such as sepsis. Supported by Ferring Research Institute Inc.